Search results for " modulators"

Therapeutic dosages of raloxifene do not modify myeloperoxidase and F2alpha-isoprostane levels in postmenopausal women.

2005

We investigated the effect of a therapeutic dose of raloxifene on the plasma levels of myeloperoxidase and F2alpha-isoprostanes, two markers of oxidative stress recently described as reliable indicators of coronary heart disease. Contrary to changes described in the literature for estrogens (E), raloxifene did not modify the levels of either myeloproxidase or F2alpha-isoprostanes after 3 or 6 months of treatment.

Are the serum levels of sCD40L modified by raloxifene in postmenopausal women?

2008

Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.

2004

OBJECTIVE Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. DESIGN Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzy…

The adverse effects of estrogen and selective estrogen receptor modulators on hemostasis and thrombosis.

2012

Agonists of the estrogen receptor include estrogens and selective estrogen receptor modulators (SERMs). Both types of compounds increase the risk for thrombosis in the arterial and the venous tree. The magnitude of the effect is influenced by potency, which depends on the type of compound and the dose. The particulars of the process change in each territory. Atherosclerosis, which creates local inflammatory conditions, may favor thrombogenesis in arteries. A direct effect of estrogen agonists is also well endorsed at both arteries, as suggested from data with high-estrogenic contraceptives, and veins. Dose reduction has been proved to be an effective strategy, but there is debate on whether…

Periodic time-domain modulation for the electrically tunable control of optical pulse train envelope and repetition rate multiplication

2012

An electrically tunable system for the control of optical pulse sequences is proposed and demonstrated. It is based on the use of an electrooptic modulator for periodic phase modulation followed by a dispersive device to obtain the temporal Talbot effect. The proposed configuration allows for repetition rate multiplication with different multiplication factors and with the simultaneous control of the pulse train envelope by simply changing the electrical signal driving the modulator. Simulated and experimental results for an input optical pulse train of 10 GHz are shown for different multiplication factors and envelope shapes. © 2006 IEEE.

Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

2021

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…

Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.

2007

Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.

Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…

2008

Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.

Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors

2006

2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis.

Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.

2011

International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…